S14. ANALYSIS OF METHYLATION AGE AND BLOOD CELL COMPOSITION IN SUBJECTS WITH CURRENT SUICIDE IDEATION

Abstract Background Suicidal Ideation (SI) remain an important and common risk factor affecting people with SCZ, who eventually attempt or complete suicide. Then the question is, what if factors (such as stressful life events and related molecular biomarkers) known to be involved in the aetiology of SCZ could help in predicting SI in this population? The accelerated aging hypothesis of SCZ posits that physiological changes associated with normal aging occur at an earlier age in individuals with SCZ than in the general population. Importantly, epigenetic changes may constitute an important component of aging process. Based on this, the chronological age can be predicted by the epigenetic clock in a highly consistent manner. The aims of this research were to determine the effect chronological and biological age on current SI and secondly, to determine the effect of the variation of cellular blood cell composition on current SI. Methods A total of 103 participants with a DSM-IV diagnosis of schizophrenia spectrum and other psychotic disorders were recruited from the Center of Addiction and Mental Health. The SI was assessed by the Columbia-Suicide Severity Rating Scale. Genome-wide DNA methylation analysis was generated from whole blood cells. The DNA methylation was assessed using the Illumina Infinium HumanMethylation450 Bead Chip while the DNA methylation-based age prediction and white blood cell composition were performed using the statistical pipeline developed by Horvath. Results Out of 103 participants, 18 had current SI (17%) while 85 had NSI. The DNAm age correlated with chronological age in the overall sample (r=0.814, p<0.0001), NSI (r=0.823, p<0.0001) and SI subjects (r=0.734, p=0.001). The strong linear relationship between DNAm age and chronological age showed a high accuracy of the epigenetic clock. However, DNAm age acceleration residuals did not differ between NSI and SI groups (t=1.532, p= 0.129). Comparison of the cellular cell blood composition between the NSI and SI groups indicated no significant differences between the NSI and SI groups (lymphocytes (t= -0.338, p=0.736), monocytes (t=-1.405, p=0.163) and granulocytes (t=0.924, p=0.358)). Furthermore, there were no significant differences between the SI and NSI groups in the analysis of the plasmablast (t=0.138, p=0.890), CD4 naïve (t=0.010, p=0.992) and CD8 naïve (t=0.681, p=0.497) Discussion Stressful life events may change DNA methylation, which in turn can affect suicide ideation and suicidal behavior. Although SCZ is associated with age-related physiological factors, we were unable to find accelerated aging in our study. Nevertheless, we cannot rule out the possibility of other aging mechanism independent of epigenetic aging in SCZ patients. Conclusion: Further studies aimed at investigating the accelerated aging hypothesis in peripheral tissue are warranted to identify individuals with SCZ at risk for suicide. This will permit a tailored treatment and will prevent suicide in SCZ individuals.

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Castration delays epigenetic aging and feminises DNA methylation at androgen-regulated loci

10.1101/2020.11.16.385369 ◽

2020 ◽

Author(s):

VJ Sugrue ◽

JA Zoller ◽

P Narayan ◽

AT Lu ◽

OJ Ortega-Recalde ◽

...

Keyword(s):

Dna Methylation ◽

Mammalian Species ◽

Accelerated Aging ◽

Absolute Error ◽

Ovis Aries ◽

Chronological Age ◽

Epigenetic Clock ◽

Mouse Muscle ◽

Aging Rate ◽

Cpg Dinucleotides

SUMMARYIn mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age using only DNA methylation data. These clocks have been used to identify novel factors influencing the aging rate, but few studies have examined the performance of epigenetic clocks in divergent mammalian species. In this study, we developed the first epigenetic clock for domesticated sheep (Ovis aries), and using 185 CpG sites can predict chronological age with a median absolute error of 5.1 months from ear punch and blood samples. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens. Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Many of these androgen sensitive demethylating sites are regulatory in nature and located in genes with known androgen-dependent regulation, such as MKLN1, LMO4 and FN1. Comparable sex-specific methylation differences in MKLN1 also exist in mouse muscle (p=0.003) but not blood, indicating that androgen dependent demethylation exists in multiple mammalian groups, in a tissue-specific manner. In characterising these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging.

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Risk of Suicidal Behavior in Children and Adolescents Exposed to Maltreatment: The Mediating Role of Borderline Personality Traits and Recent Stressful Life Events

Journal of Clinical Medicine ◽

10.3390/jcm10225293 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5293

Author(s):

Laia Marques-Feixa ◽

Jorge Moya-Higueras ◽

Soledad Romero ◽

Pilar Santamarina-Pérez ◽

Marta Rapado-Castro ◽

...

Keyword(s):

Children And Adolescents ◽

Life Events ◽

Suicidal Behavior ◽

Emotion Dysregulation ◽

Structural Equation ◽

Stressful Life Events ◽

Suicide Ideation ◽

Borderline Personality ◽

Stressful Life ◽

Targeted Interventions

Childhood maltreatment (CM) is associated with increased non-suicidal self-injury (NSSI) and suicidal behavior (SB), independently of demographic and mental health conditions. Self-Trauma Theory and Linehan’s Biopsychosocial Model might explain the emergence of Borderline Personality Disorder (BPD) symptoms as mediators of the association between CM and the risk of SB. However, little is known regarding such relationships when the exposure is recent for young persons. Here, we study 187 youths aged 7–17, with or without mental disorders. We explore CM experiences (considering the severity and frequency of different forms of neglect and abuse), recent stressful life events (SLEs), some BPD traits (emotion dysregulation, intense anger and impulsivity), and the risk of SB (including NSSI, suicide threat, suicide ideation, suicide plan and suicide attempt). We study the direct and mediating relationships between these variables via a structural equation analysis using the statistical software package EQS. Our findings suggest that youths exposed to more severe/frequent CM have more prominent BPD traits, and are more likely to have experienced recent SLEs. In turn, BPD traits increase the risk of SLEs. However, only emotion dysregulation and recent SLEs were found to be correlated with SB. Therefore, targeted interventions on emotion dysregulation are necessary to prevent NSSI or SB in children and adolescents exposed to CM, as is the minimization of further SLEs.

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Child maltreatment, recent stressful life events, and suicide ideation: A test of the stress sensitivity hypothesis

Child Abuse & Neglect ◽

10.1016/j.chiabu.2020.104926 ◽

2021 ◽

Vol 113 ◽

pp. 104926

Author(s):

Erinn B. Duprey ◽

Elizabeth D. Handley ◽

Jody Todd Manly ◽

Dante Cicchetti ◽

Sheree L. Toth

Keyword(s):

Child Maltreatment ◽

Life Events ◽

Stressful Life Events ◽

Suicide Ideation ◽

Stress Sensitivity ◽

Stressful Life

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Positive Mental Health, Stressful Life Events, and Suicide Ideation

Crisis ◽

10.1027/0227-5910/a000652 ◽

2020 ◽

Vol 41 (5) ◽

pp. 383-388 ◽

Cited By ~ 5

Author(s):

Julia Brailovskaia ◽

Tobias Teismann ◽

Jürgen Margraf

Keyword(s):

Mental Health ◽

Life Events ◽

Stressful Life Events ◽

Suicide Ideation ◽

Well Being ◽

Positive Mental Health ◽

Self Report ◽

Stressful Life ◽

Hierarchical Regression ◽

The Impact

Abstract. Background: Stressful life events and suicide ideation regularly occur together. Yet, little is known about factors that buffer individuals against the development of suicide ideation. Aim: In a long-term follow-up study design, it was investigated whether positive mental health, that is, high levels of subjective and psychological well-being, buffers the association between stressful life events and suicide ideation. Method: A total of 126 German students (80.2% female; age: M = 24.29, SD = 5.21) were assessed at a baseline evaluation and again 24 months later. Data were collected using self-report questionnaires. Results: Linear hierarchical regression analysis was used to analyze the data. Positive mental health was considered to moderate the impact of stressful life events on suicide ideation – controlling for age and gender. Limitations: Current results are limited to university students. Conclusions: Positive mental health interacts with stressful life events, such that those with high levels of positive mental health show an attenuated increase in suicide ideation at elevated levels of stress. Positive mental health seems to confer resilience and should be focused on in counseling centers for students.

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